Cefuroxime is a cephalosporin antibiotic with a broad spectrum of activity against both gram-positive and gram-negative microorganisms. Due to poor absorption from the gastrointestinal tract following oral administration, its salt, cefuroxime sodium, is ideally suited to formulation as injectables. The need for a more convenient and broader therapeutic use of cefuroxime led to the synthesis of 1-acetoxyethyl ester of cefuroxime, which is referred to as cefuroxime axetil. Cefuroxime axetil is a prodrug of cefuroxime and is suitable for oral administration. As a result, it permits a more convenient and broader therapeutic use of cefuroxime.
Cefuroxime axetil possesses an asymmetric carbon atom at the 1-position of the 1-acetoxyethyl group and, therefore, can exist as R- and S-isomers and mixtures thereof. Cefuroxime axetil is marketed as a mixture of R- and S-isomers in an approximately 1:1 ratio.
While cefuroxime axetil well suited to formulation for oral administration, it suffers from several deficiencies. Cefuroxime axetil is rapidly hydrolyzed in the intestine, thereby resulting in the formation of cefuroxime, which is poorly absorbed from the gastrointestinal tract. It has also been observed that oral administration of the R,S-mixture results in only about 50% bioavailability of the cefuroxime antibiotic, which is due to low overall solubility and the rapid hydrolysis of the ester portion of cefuroxime axetil by the esterase enzyme located in the gut. The non-absorbable cefuroxime remaining in the gut accounts for a partial loss of therapeutic activity and possibly the cause of side effects generally observed.
The rate of cleavage of ester group of the individual R- and S-isomers of cefuroxime axetil by esterase enzyme is different and it has been discovered that the individual S-isomer is hydrolyzed in animals much more rapidly than the R-isomer. U.S. Pat. No. 5,063,224 provides a process for preparing substantially pure R-cefuroxime axetil. It embodies the invention by claiming the superior stability to esterases and greater bioavailability of R-cefuroxime axetil over S-isomer, thus reducing the amount of non-absorbable cefuroxime remaining in the gut lumen, thereby diminishing the side effects attributable to cefuroxime. However, said patent does not describe the use of the undesirable S-isomer. Accordingly, there has been a need for a process whereby the undesirable S-isomer could be recycled. Such a process would not only be useful in minimizing the waste should R-cefuroxime axetil be used as a drug, but also be advantageous from a commercial standpoint.